Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2

Autores
Ogonowski, Natalia Soledad; Santamaria Garcia, Hernando; Baez, Sandra; Lopez, Andrea; Laserna, Andrés; Garcia Cifuentes, Elkin; Ayala Ramirez, Paola; Zarante, Ignacio; Suarez Obando, Fernando; Reyes, Pablo; Kauffman, Marcelo Andres; Cochran, Nick; Schulte, Michael; Sirkis, Daniel W; Spina, Salvatore; Yokoyama, Jennifer S; Miller, Bruce L; Kosik, Kenneth; Matallana, Diana; Ibáñez, Santiago Agustín
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). Methods To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups - a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). Results The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. Conclusion In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.
Fil: Ogonowski, Natalia Soledad. Universidad Adolfo Ibáñez; Chile
Fil: Santamaria Garcia, Hernando. Pontificia Universidad Javeriana; Colombia. Hospital Universitario San Ignacio; Colombia. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baez, Sandra. Universidad de los Andes; Colombia
Fil: Lopez, Andrea. Fundacion Santa Fe de Bogota; Colombia. Pontificia Universidad Javeriana; Colombia
Fil: Laserna, Andrés. Pontificia Universidad Javeriana; Colombia. University of Rochester Medical Center; Estados Unidos
Fil: Garcia Cifuentes, Elkin. Hospital Universitario San Ignacio; Colombia. Pontificia Universidad Javeriana; Colombia
Fil: Ayala Ramirez, Paola. Pontificia Universidad Javeriana; Colombia
Fil: Zarante, Ignacio. Pontificia Universidad Javeriana; Colombia
Fil: Suarez Obando, Fernando. Pontificia Universidad Javeriana; Colombia
Fil: Reyes, Pablo. Pontificia Universidad Javeriana; Colombia
Fil: Kauffman, Marcelo Andres. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Cochran, Nick. Hudsonalpha Institute For Biotechnology; Estados Unidos
Fil: Schulte, Michael. Brainlat; Chile
Fil: Sirkis, Daniel W. University of California; Estados Unidos
Fil: Spina, Salvatore. University of California; Estados Unidos
Fil: Yokoyama, Jennifer S. University of California; Estados Unidos
Fil: Miller, Bruce L. University of California; Estados Unidos
Fil: Kosik, Kenneth. University of California; Estados Unidos
Fil: Matallana, Diana. Fundacion Santa Fe de Bogota; Colombia. Pontificia Universidad Javeriana; Colombia
Fil: Ibáñez, Santiago Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Trinity College Dublin; Irlanda. Universidad Adolfo Ibañez; Chile. Universidad de San Andrés. Rectorado. Centro de Neurociencias Cognitivas;
Materia
GENETICS
NEURODEGENERATIVE DISEASES
NEUROLOGY
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/224693
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/224693
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network_name_str CONICET Digital (CONICET)
spelling Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2Ogonowski, Natalia SoledadSantamaria Garcia, HernandoBaez, SandraLopez, AndreaLaserna, AndrésGarcia Cifuentes, ElkinAyala Ramirez, PaolaZarante, IgnacioSuarez Obando, FernandoReyes, PabloKauffman, Marcelo AndresCochran, NickSchulte, MichaelSirkis, Daniel WSpina, SalvatoreYokoyama, Jennifer SMiller, Bruce LKosik, KennethMatallana, DianaIbáñez, Santiago AgustínGENETICSNEURODEGENERATIVE DISEASESNEUROLOGYhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). Methods To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups - a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). Results The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. Conclusion In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.Fil: Ogonowski, Natalia Soledad. Universidad Adolfo Ibáñez; ChileFil: Santamaria Garcia, Hernando. Pontificia Universidad Javeriana; Colombia. Hospital Universitario San Ignacio; Colombia. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Baez, Sandra. Universidad de los Andes; ColombiaFil: Lopez, Andrea. Fundacion Santa Fe de Bogota; Colombia. Pontificia Universidad Javeriana; ColombiaFil: Laserna, Andrés. Pontificia Universidad Javeriana; Colombia. University of Rochester Medical Center; Estados UnidosFil: Garcia Cifuentes, Elkin. Hospital Universitario San Ignacio; Colombia. Pontificia Universidad Javeriana; ColombiaFil: Ayala Ramirez, Paola. Pontificia Universidad Javeriana; ColombiaFil: Zarante, Ignacio. Pontificia Universidad Javeriana; ColombiaFil: Suarez Obando, Fernando. Pontificia Universidad Javeriana; ColombiaFil: Reyes, Pablo. Pontificia Universidad Javeriana; ColombiaFil: Kauffman, Marcelo Andres. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Cochran, Nick. Hudsonalpha Institute For Biotechnology; Estados UnidosFil: Schulte, Michael. Brainlat; ChileFil: Sirkis, Daniel W. University of California; Estados UnidosFil: Spina, Salvatore. University of California; Estados UnidosFil: Yokoyama, Jennifer S. University of California; Estados UnidosFil: Miller, Bruce L. University of California; Estados UnidosFil: Kosik, Kenneth. University of California; Estados UnidosFil: Matallana, Diana. Fundacion Santa Fe de Bogota; Colombia. Pontificia Universidad Javeriana; ColombiaFil: Ibáñez, Santiago Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Trinity College Dublin; Irlanda. Universidad Adolfo Ibañez; Chile. Universidad de San Andrés. Rectorado. Centro de Neurociencias Cognitivas;B M J Publishing Group2023-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/224693Ogonowski, Natalia Soledad; Santamaria Garcia, Hernando; Baez, Sandra; Lopez, Andrea; Laserna, Andrés; et al.; Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2; B M J Publishing Group; Journal Of Medical Genetics; 60; 9; 9-2023; 894-9040022-2593CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://jmg.bmj.com/lookup/doi/10.1136/jmg-2022-108627info:eu-repo/semantics/altIdentifier/doi/10.1136/jmg-2022-108627info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:14:25Zoai:ri.conicet.gov.ar:11336/224693instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:14:25.769CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
title Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
spellingShingle Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
Ogonowski, Natalia Soledad
GENETICS
NEURODEGENERATIVE DISEASES
NEUROLOGY
title_short Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
title_full Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
title_fullStr Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
title_full_unstemmed Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
title_sort Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
dc.creator.none.fl_str_mv Ogonowski, Natalia Soledad
Santamaria Garcia, Hernando
Baez, Sandra
Lopez, Andrea
Laserna, Andrés
Garcia Cifuentes, Elkin
Ayala Ramirez, Paola
Zarante, Ignacio
Suarez Obando, Fernando
Reyes, Pablo
Kauffman, Marcelo Andres
Cochran, Nick
Schulte, Michael
Sirkis, Daniel W
Spina, Salvatore
Yokoyama, Jennifer S
Miller, Bruce L
Kosik, Kenneth
Matallana, Diana
Ibáñez, Santiago Agustín
author Ogonowski, Natalia Soledad
author_facet Ogonowski, Natalia Soledad
Santamaria Garcia, Hernando
Baez, Sandra
Lopez, Andrea
Laserna, Andrés
Garcia Cifuentes, Elkin
Ayala Ramirez, Paola
Zarante, Ignacio
Suarez Obando, Fernando
Reyes, Pablo
Kauffman, Marcelo Andres
Cochran, Nick
Schulte, Michael
Sirkis, Daniel W
Spina, Salvatore
Yokoyama, Jennifer S
Miller, Bruce L
Kosik, Kenneth
Matallana, Diana
Ibáñez, Santiago Agustín
author_role author
author2 Santamaria Garcia, Hernando
Baez, Sandra
Lopez, Andrea
Laserna, Andrés
Garcia Cifuentes, Elkin
Ayala Ramirez, Paola
Zarante, Ignacio
Suarez Obando, Fernando
Reyes, Pablo
Kauffman, Marcelo Andres
Cochran, Nick
Schulte, Michael
Sirkis, Daniel W
Spina, Salvatore
Yokoyama, Jennifer S
Miller, Bruce L
Kosik, Kenneth
Matallana, Diana
Ibáñez, Santiago Agustín
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GENETICS
NEURODEGENERATIVE DISEASES
NEUROLOGY
topic GENETICS
NEURODEGENERATIVE DISEASES
NEUROLOGY
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). Methods To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups - a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). Results The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. Conclusion In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.
Fil: Ogonowski, Natalia Soledad. Universidad Adolfo Ibáñez; Chile
Fil: Santamaria Garcia, Hernando. Pontificia Universidad Javeriana; Colombia. Hospital Universitario San Ignacio; Colombia. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Baez, Sandra. Universidad de los Andes; Colombia
Fil: Lopez, Andrea. Fundacion Santa Fe de Bogota; Colombia. Pontificia Universidad Javeriana; Colombia
Fil: Laserna, Andrés. Pontificia Universidad Javeriana; Colombia. University of Rochester Medical Center; Estados Unidos
Fil: Garcia Cifuentes, Elkin. Hospital Universitario San Ignacio; Colombia. Pontificia Universidad Javeriana; Colombia
Fil: Ayala Ramirez, Paola. Pontificia Universidad Javeriana; Colombia
Fil: Zarante, Ignacio. Pontificia Universidad Javeriana; Colombia
Fil: Suarez Obando, Fernando. Pontificia Universidad Javeriana; Colombia
Fil: Reyes, Pablo. Pontificia Universidad Javeriana; Colombia
Fil: Kauffman, Marcelo Andres. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Cochran, Nick. Hudsonalpha Institute For Biotechnology; Estados Unidos
Fil: Schulte, Michael. Brainlat; Chile
Fil: Sirkis, Daniel W. University of California; Estados Unidos
Fil: Spina, Salvatore. University of California; Estados Unidos
Fil: Yokoyama, Jennifer S. University of California; Estados Unidos
Fil: Miller, Bruce L. University of California; Estados Unidos
Fil: Kosik, Kenneth. University of California; Estados Unidos
Fil: Matallana, Diana. Fundacion Santa Fe de Bogota; Colombia. Pontificia Universidad Javeriana; Colombia
Fil: Ibáñez, Santiago Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Trinity College Dublin; Irlanda. Universidad Adolfo Ibañez; Chile. Universidad de San Andrés. Rectorado. Centro de Neurociencias Cognitivas;
description Background The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). Methods To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups - a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). Results The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. Conclusion In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.
publishDate 2023
dc.date.none.fl_str_mv 2023-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/224693
Ogonowski, Natalia Soledad; Santamaria Garcia, Hernando; Baez, Sandra; Lopez, Andrea; Laserna, Andrés; et al.; Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2; B M J Publishing Group; Journal Of Medical Genetics; 60; 9; 9-2023; 894-904
0022-2593
CONICET Digital
CONICET
url http://hdl.handle.net/11336/224693
identifier_str_mv Ogonowski, Natalia Soledad; Santamaria Garcia, Hernando; Baez, Sandra; Lopez, Andrea; Laserna, Andrés; et al.; Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2; B M J Publishing Group; Journal Of Medical Genetics; 60; 9; 9-2023; 894-904
0022-2593
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1136/jmg-2022-108627
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv B M J Publishing Group
publisher.none.fl_str_mv B M J Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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